Carrageenan-Containing Gel in Reducing the Rate of HPV Infection in Healthy Participants

PRIMARY OBJECTIVES:

I. To measure the overall efficacy of the intervention in reducing the rate of incident
cervical HPV infection.

SECONDARY OBJECTIVES:

I. Perform in vitro exploratory testing of how long after vaginal application the drug
retains biological activity by collecting cervicovaginal lavage (CVL) at different times and
spiking the samples with HPV pseudovirions (PsVs) and measuring PsV entry into target cells.

II. These studies will be expanded to test multiple HPV types and to examine whether the
anti-HPV activity of the intervention is preserved in the setting of semen.

III. Store swabs to potentially test candidate biomarkers of microbicide efficacy and safety.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants apply carrageenan-containing gel vaginally within 12 hours prior to each
vaginal sex act and as soon as possible within 12 hours after each vaginal sex act and use
condoms for 12 months.

ARM II: Participants apply placebo gel vaginally within 12 hours prior to each vaginal sex
act and as soon as possible within 12 hours after each vaginal sex act and use condoms for 12
months.

Inclusion Criteria:

- Sexually active women of all ethnicities and races with an intact cervix are eligible
for this trial

- Engaging in three or more intercourse events (defined as having penile-vaginal
intercourse) per month; subjects must consent not to douche or use any vaginal
products, including tampons, for 24 hours before enrollment and study visits

- Normal Pap or Atypical Squamous Cells of Undetermined Significance (ASCUS) Pap test
with HPV deoxyribonucleic acid (DNA) negative by reflex testing via Hybrid Capture 2
(Digene Corp., Gaithersburg, MD), a standard clinical assay within clinically
acceptable screening guidelines (American Cancer Society [ACS]/American Society for
Colposcopy and Cervical Pathology [ASCCP] 2012 Screening Guidelines)

- Using an adequate method of contraception for at least 3 months with no changes and
will remain on the contraception for the duration of the trial; an adequate method of
contraception is defined as either a hormonal based method (except vaginal rings); an
intrauterine device (IUD) (inserted at least 30 days prior to enrollment); female
sterilization; or sexual activity with a partner who had a vasectomy

- Speaks either English or Spanish, living in or near Newark with no plans to move in
the next year, able to sign consent and complete questionnaires with aid of trained
personnel

Exclusion Criteria:

- Prior use of an HPV vaccine

- Women in the vaccine-eligible age range cannot have received vaccine prior to
enrollment, but will be offered HPV vaccination at the end of the study; in
brief, we are interested in the efficacy of intervention in preventing HPV in the
absence of HPV vaccination, since most women worldwide who might utilize
intervention will not have been vaccinated; this includes United States (US)
women in the vaccine "catch-up" 19-26 year old age group (beyond the age groups
eligible for Vaccines for Children- funded vaccination) who have so far had very
low (< 10%) vaccine uptake; it also includes the entire group of US women > 26
years of age; moreover, it includes women of all ages in developing countries,
who most need an HPV prevention strategy, but may never be vaccinated; it should
be noted that delaying vaccination in women 19-26 years of age by one year is
safe and reasonable, since there is insufficient data to establish a
recommendation for or against universal vaccination in this age group as
concluded by an American Cancer Society expert panel, which includes the
Principal Investigator (PI) of this protocol, Dr. Mark Einstein; it is
anticipated that if the intervention gel is efficacious, HPV vaccinated women
would need to be studied in a similar future trial with power analysis taking
into account vaccine effectiveness as well

- Any previous surgical excision of cervical intraepithelial neoplasia (CIN) or
hysterectomy

- A serious, concomitant disorder, including active systemic infection requiring
treatment

- Prior history of or current malignancy other than adequately treated skin cancer
(squamous cell cancer or basal cell carcinoma)

- Documented or suspected immunosuppressive disorder or autoimmune disease

- Any significant cardiac, hepatic or renal disease

- Pregnant and/or breast-feeding

- Recent (within 4 weeks of screening) or concomitant long term treatment with systemic
steroids, immunosuppressive/immunomodulating drugs (e.g. cyclosporine,
corticosteroids)

- Intranasal, inhaled and/or topical steroids are permissible

- Documented human immunodeficiency virus (HIV) infection, genital warts, chancroid, or
pelvic inflammatory disease that will require long term treatment

- Active genital ulcers

- Use of an investigational drug in the 3 months prior to screening and must agree to
not participate in any drug or device study while enrolled in this study

- Any known allergy or hypersensitivity to vaginal lubricants or any component of study
product